Reagent control of stereoselectivity

These reagents exhibit reagent control of stereoselectivity and have proven to be very useful in stereoselective synthesis of polyketide natural products, which frequently contain arrays of alternating methyl and oxygen substituents.44... 

BBN effects the hydration of the C=C double bond of 1-methylcyclohexene according to Figure 3.25 in such a way that after the oxidative workup, racemic 2-methyl-l-cyclohexanol is obtained. This brings up the question Is an enantioselective H20 addition to the same alkene possible The answer is yes, but only with the help of reagent control of stereoselectivity (cf. Section 3.4.2). 

Our earlier statements on substrate and reagent control of stereoselectivity during hydro-borations are incorporated in Figure 3.31. Because of the obvious analogies between the old and the new reactions, the following can be predicted about the product distribution shown ... 

The condition for the occurrence of a mutual kinetic resolution is therefore that considerable substrate control of stereoselectivity and considerable reagent control of stereoselectivity occur simultaneously. 

For the discussion in Sections 3.4.4 and 3.4.5, we will assume ( ) that k6 > k7 that is, the reagent control of stereoselectivity is more effective than the substrate control of stereoselectivity. The justification for this assumption is simply that it makes additional thought experiments possible. These are useful for explaining interesting phenomena associated with stereoselective synthesis, which are known from other reactions. Because the thought experiments are much easier to understand than many of the actual experiments, their presentation is given preference for introducing concepts. 

Fig. 3.31. Thought experiment I products from the addition of a racemic chiral dialkylborane to a racemic chiral alkene. Rectangular boxes previously discussed reference reactions for the effect of substrate control (top box reaction from Figure 3.26) or reagent control of stereoselectivity [leftmost box reaction from Figure 3.30 (rewritten for racemic instead of enantiomer-ically pure reagent)]. Solid reaction arrows, reagent control of stereoselectivity dashed reaction arrows, substrate control of stereoselectivity red reaction arrows (kinetically favored reactions), reactions proceeding with substrate control (solid lines) or reagent control (dashed lines) of stereoselectivity black reaction arrows (kinetically disfavored reactions), reactions proceeding opposite to substrate control (solid lines) or reagent control (dashed lines) of stereoselectivity.

At the beginning of Section 3.4, we wondered whether 3-ethyl-l-methylcyclohexene could also be hydroborated/oxidized/hydrolyzed to furnish the cis, trans-con 11 gured alcohol. There is a solution (Figure 3.32) if two requirements are fulfilled. First, we must rely on the assumption made in Section 3.4.3 that this atkene reacts with the cyclic borane in such a way that the reagent control of stereoselectivity exceeds the substrate control of the stereoselectivity. Second, both the alkene and the borane must be used in enantiomerically pure form. 

Fig. 3. 32. Thought experiment II reagent control of stereoselectivity as a method for imposing on the substrate a diastereoselectivity that is alien to it (mismatched pair situation).

BBN attacks the C=C double bond of 3-ethyl-l-methylcyclohexene according to Figure 3.20 exclusively from the side that lies opposite the ethyl group at the stereocenter. Consequently, after oxidation and hydrolysis, a fra s,fra s-configured alcohol is produced. The question that arises is Can this diastereoselectivity be reversed in favor of the cis,trans isomer The answer is possibly, but, if so, only by using reagent control of stereoselectivity (cf. Section 3.4.4). 

In the structure shown in Figure 3.24 the top side attack of this borane on the C=C double bond of 1-methylcyclohexene prevails kinetically over the bottom side attack. This is because only the top side attack of the boranes avoids steric interactions between the methyl substituents on the borane and the six-membered ring. In other words, the reagent determines the face to which it adds. We thus have reagent control of stereoselectivity. As a result, the mixture of the diastereomeric trialkylboranes C and D, both of which are pure enantiomers, is produced with ds = 97.8 2.2. After the normal Na0H/H202 treatment, they give a 97.8 2.2 mixture of the enantiomeric trans-2-... 

Fig. 3.27. Thought experiment III Reagent control of stereoselectivity as a method for enhancing the substrate control of stereoselectivity (matched pair situation).

Scheme 10.20 Method-oriented construction of the neighboring stereogenic centers in erythronolide A, featuring reagent control of stereoselectivity...

Scheme 10.21 Reagent control of stereoselectivity during the skeletal bond-forming steps in the synthesis of erythronolide A...

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